Feasibility Study of Exenatide by Continuous Subcutaneous Infusion

NCT01857895 | Completed Phase 1

• 1 other identifier: 200016
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label study to investigate the feasibility of administering exenatide by continuous subcutaneous infusion to healthy subjects. Study will consist of two parts i.e. Part A and B. In Part A 2 healthy subjects will receive exenatide infusion over 24 hours followed by a follow-up visit 10 to 14 days after discharge from clinic. In Part B approximately 6 healthy subjects will receive subcutaneous infusions of exenatide for maximum of 7 days followed by a follow-up visit 10 to 14 days after discharge from clinic.

Conditions

Obesity

Keywords

Nausea; subcutaneous infusion; exenatide

Outcome Measures

Primary Outcomes (9)

• Characterization of interruptions or deviations from prescribed exenatide infusion in Part A

  To investigate the feasibility of administering exenatide via continuous subcutaneous infusion

  2 days

• Characterization of interruptions or deviations from prescribed exenatide infusion in Part B

  To investigate the feasibility of administering exenatide via continuous subcutaneous infusion

  8 days

• Infusion rate adjustments when nausea/vomiting occurs in Part B

  To investigate the feasibility of administering exenatide via continuous subcutaneous infusion. Infusion rate adjustment will be done to achieve tolerable infusion rate when nausea/vomiting occurs

  8 days

• Number of participants with adverse events (AEs) in Part A

  AEs will be collected from the Day -1 and until the follow-up contact. AE data will be collected to evaluate the ability to monitor and maintain acceptable safety

  17 days

• Number of participants with AEs in Part B

  AEs will be collected from the Day -1 and until the follow-up contact. AE data will be collected to evaluate the ability to monitor and maintain acceptable safety

  23 days

• Laboratory parameter assessment in Part A

  Laboratory parameters include: hematology, clinical chemistry, and urinalysis

  17 days

• Laboratory parameter assessment in Part B

  Laboratory parameters include: hematology, clinical chemistry, and urinalysis

  23 days

• Vital sign assessment in Part A

  Vital signs measurement include: systolic and diastolic blood pressure, and pulse rate

  17 days

• Vital sign assessment in Part B

  Vital signs measurement include: systolic and diastolic blood pressure, and pulse rate

  23 days

Secondary Outcomes (2)

• Pharmacokinetic (PK) profile of exenatide in Part A

  PK samples will be collected at pre-dose, and at 0.5, 1, 2, 4, 6, 10, 14, 24, and 26 hours post dose.

• Pharmacokinetic (PK) profile of exenatide in Part B

  8 days

Study Arms (2)

Exenatide infusion in Part A

EXPERIMENTAL

Subjects in Part A will receive exenatide as a subcutaneous infusion at a constant rate for 24 hours.

Drug: Exenatide

Exenatide infusion in Part B

EXPERIMENTAL

Subjects in Part B will receive exenatide with daily increases in the infusion rate.

Drug: Exenatide

Interventions

Exenatide DRUG

Prefilled pen containing 2.4 mL of drug will be transferred into MiniMed Paradigm Real-Time Revel device for subcutaneous infusion.

Exenatide infusion in Part A; Exenatide infusion in Part B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male/females aged between 18 and 60 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body Mass Index within the range 18 to 35 kilograms/meter squared (kg/m\^2) inclusive.
• A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone \> 40 milli international unit/mililiter (mL) and estradiol \<40 picogram/mL (\<147 picomoles/Liter) is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
• Child-bearing potential females must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until follow up visit.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Based on QT interval corrected for heart rate (QTc) of single electrocardiogram (ECG): QTc by Fridericia's formula \<450 millisecond (msec).
• Aspartate aminotransferase and Alanine aminotransferase \<2x upper limit of normal (ULN); alkaline phosphatase and bilirubin \<= 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Subjects with a personal or family history of thyroid carcinoma or Type 2 Familial Endocrine Neoplasia.
• History of uncorrected thyroid dysfunction or an abnormal thyroid functions as assessed by thyroid stimulating hormones.
• Subjects with a history of severe gastrointestinal disease, or abnormal renal function.
• Subjects with previous exposure to a Glucagon-like peptide-1 mimetic.
• History of chronic or acute pancreatitis. Note: Subjects with a lipase value above 1.5X ULN at screening are excluded.
• Current or chronic history of liver disease, or hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Parexel: collaborator

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Vlasakakis G, Johnson SL, Lin J, Yao X, Gruenloh CJ, Chism JP, Nunez DJ. Pharmacokinetics and Tolerability of Exenatide Delivered by 7-Day Continuous Subcutaneous Infusion in Healthy Volunteers. Adv Ther. 2015 Jul;32(7):650-61. doi: 10.1007/s12325-015-0222-4. Epub 2015 Jul 10.

  PMID: 26160357 DERIVED

Related Links

• Results for study 200016 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Obesity; Nausea

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 20, 2013
• Study Start: May 16, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: October 19, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)